title: The effect of transient increases in kynurenic acid and quinolinic acid levels early in life on behavior in adulthood: Implications for schizophrenia.
abstract: Kynurenic acid is a tryptophan metabolite that is synthesized and released in the brain by astrocytes and acts as an antagonist of nicotinic acetylcholine receptors and N-methyl-d-aspartate glutamate receptors, both of which are critically involved in cognition as well as neural plasticity and brain development. The concentration of kynurenic acid is increased in the brains of persons with schizophrenia and this increase has been implicated in the cognitive and social impairments associated with the disease. In addition, growing evidence suggests that the increase in kynurenic acid may begin early in life. For example, exposure to influenza A virus during development results in a transient increase in kynurenic acid concentration that could disrupt normal brain development and lead to cognitive deficits later in life. Changes in kynurenic acid may thus provide a link between developmental exposure to viruses and the increased risk of subsequently developing schizophrenia. To test this, we mimicked the effects of influenza A exposure by treating rats with kynurenine, the precursor of kynurenic acid, on postnatal days 7-10. We observed a transient increase in both kynurenic acid and quinolinic acid during treatment. When rats were subsequently behaviorally tested as adults, those previously treated with kynurenine exhibited decreased social behavior and locomotor activity. In contrast, attentional function and fear conditioning were not affected. Together with other recent findings, these data have several implications for understanding how viral-induced changes in tryptophan metabolism during development may contribute to schizophrenia-related symptoms later in life.
authors.affiliation: Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH 03755, United States.
authors.forename: Hannah F
authors.initials: HF
authors.lastname: Iaccarino
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Suckow
authors.forename: Shan
authors.initials: S
authors.lastname: Xie
authors.forename: David J
authors.initials: DJ
authors.lastname: Bucci
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001288:Attention / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D015331:Cohort Studies; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects; D005260:Female; D007398:Interpersonal Relations; D007736:Kynurenic Acid / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D018691:Excitatory Amino Acid Antagonists; D017378:Quinolinic Acid; D007736:Kynurenic Acid
keywords: Attention; Glia; Learning; Memory; Schizophrenia; Social